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Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?

Despite tremendous progress in modern-day stroke therapy, ischemic stroke remains a disease associated with a high socioeconomic burden in industrialized countries. In light of demographic change, these health care costs are expected to increase even further. The current causal therapeutic treatment...

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Autores principales: Haupt, Matteo, Gerner, Stefan T., Bähr, Mathias, Doeppner, Thorsten R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140731/
https://www.ncbi.nlm.nih.gov/pubmed/35628192
http://dx.doi.org/10.3390/ijms23105381
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author Haupt, Matteo
Gerner, Stefan T.
Bähr, Mathias
Doeppner, Thorsten R.
author_facet Haupt, Matteo
Gerner, Stefan T.
Bähr, Mathias
Doeppner, Thorsten R.
author_sort Haupt, Matteo
collection PubMed
description Despite tremendous progress in modern-day stroke therapy, ischemic stroke remains a disease associated with a high socioeconomic burden in industrialized countries. In light of demographic change, these health care costs are expected to increase even further. The current causal therapeutic treatment paradigms focus on successful thrombolysis or thrombectomy, but only a fraction of patients qualify for these recanalization therapies because of therapeutic time window restrictions or contraindications. Hence, adjuvant therapeutic concepts such as neuroprotection are urgently needed. A bench-to-bedside transfer of neuroprotective approaches under stroke conditions, however, has not been established after more than twenty years of research, albeit a great many data have demonstrated several neuroprotective drugs to be effective in preclinical stroke settings. Prominent examples of substances supported by extensive preclinical evidence but which failed clinical trials are tirilazad and disodium 2,4-sulphophenyl-N-tert-butylnitrone (NXY-059). The NXY-059 trial, for instance, was retrospectively shown to have a seriously weak study design, a trial of insufficient quality and a poor statistical analysis, although it initially met the recommendations of the STAIR committee. In light of currently ongoing novel neuroprotective stroke trials, such as ESCAPE-NA, and to avoid the mistakes made in the past, an improvement in study quality in the field of stroke neuroprotection is urgently needed. In the present review, animal models closely reflecting the “typical” stroke patient, occlusion techniques and the appropriate choice of time windows are discussed. In this context, the STAIR recommendations could provide a useful orientation. Taking all of this into account, a new dawn for neuroprotection might be possible.
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spelling pubmed-91407312022-05-28 Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection? Haupt, Matteo Gerner, Stefan T. Bähr, Mathias Doeppner, Thorsten R. Int J Mol Sci Review Despite tremendous progress in modern-day stroke therapy, ischemic stroke remains a disease associated with a high socioeconomic burden in industrialized countries. In light of demographic change, these health care costs are expected to increase even further. The current causal therapeutic treatment paradigms focus on successful thrombolysis or thrombectomy, but only a fraction of patients qualify for these recanalization therapies because of therapeutic time window restrictions or contraindications. Hence, adjuvant therapeutic concepts such as neuroprotection are urgently needed. A bench-to-bedside transfer of neuroprotective approaches under stroke conditions, however, has not been established after more than twenty years of research, albeit a great many data have demonstrated several neuroprotective drugs to be effective in preclinical stroke settings. Prominent examples of substances supported by extensive preclinical evidence but which failed clinical trials are tirilazad and disodium 2,4-sulphophenyl-N-tert-butylnitrone (NXY-059). The NXY-059 trial, for instance, was retrospectively shown to have a seriously weak study design, a trial of insufficient quality and a poor statistical analysis, although it initially met the recommendations of the STAIR committee. In light of currently ongoing novel neuroprotective stroke trials, such as ESCAPE-NA, and to avoid the mistakes made in the past, an improvement in study quality in the field of stroke neuroprotection is urgently needed. In the present review, animal models closely reflecting the “typical” stroke patient, occlusion techniques and the appropriate choice of time windows are discussed. In this context, the STAIR recommendations could provide a useful orientation. Taking all of this into account, a new dawn for neuroprotection might be possible. MDPI 2022-05-11 /pmc/articles/PMC9140731/ /pubmed/35628192 http://dx.doi.org/10.3390/ijms23105381 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Haupt, Matteo
Gerner, Stefan T.
Bähr, Mathias
Doeppner, Thorsten R.
Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
title Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
title_full Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
title_fullStr Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
title_full_unstemmed Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
title_short Quest for Quality in Translational Stroke Research—A New Dawn for Neuroprotection?
title_sort quest for quality in translational stroke research—a new dawn for neuroprotection?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140731/
https://www.ncbi.nlm.nih.gov/pubmed/35628192
http://dx.doi.org/10.3390/ijms23105381
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